BMS 200 Async Topic 2: ADHD & Substance Use PDF

Asynchronous Topic 2 Biomedicine of: ADHD Substance Use Disorders BMS 200 ADHD - Overview Definition: neuropsychiatric condition that can affect all ages, but onset in vast majority thought to be in childhood ( < 12 years) ▪ Diminished sustained attention ▪ Increased i...

Asynchronous Topic 2 Biomedicine of: ADHD Substance Use Disorders BMS 200 ADHD - Overview Definition: neuropsychiatric condition that can affect all ages, but onset in vast majority thought to be in childhood ( < 12 years) ▪ Diminished sustained attention ▪ Increased impulsivity or hyperactivity Affects 5-8% of school-age children and nearly the same number ( 5 – 6%) of adults ▪ ~ 60% of those who are symptomatic in childhood continue to show symptoms in adulthood Three major types of presentations: ▪ Predominantly inattentive presentation ▪ Predominantly hyperactive/impulsive presentation ▪ Combined presentation DSM V – ADHD Criteria (children/ adolescents) Duration of symptoms > 6 months, symptoms present prior to age 12 Inattentive symptoms: Hyperactivity/impulsivity ▪ Poor attention to detail/ symptoms: frequent mistakes ▪ Fidgety/restless ▪ Difficulty maintaining ▪ Cannot stay seated attention/focus ▪ Runs/climbs inappropriately ▪ When spoken to, appears ▪ Cannot do activities quietly not to listen ▪ Cannot stay still ▪ Poor follow-through on tasks ▪ Inappropriately talkative ▪ Poor organizational skills ▪ Inappropriately blurts out ▪ Procrastinates from tasks answers requiring attention ▪ Cannot wait for their turn ▪ Loses things ▪ Interrupts others ▪ Distractible ▪ Forgetfulness DSM V – ADHD Criteria (children/ adolescents) Several of the inattentive or hyperactive-impulsive symptoms need to be present in two or more settings (work, friends, school, home, extracurricular activities, etc.) Symptoms interfere with (or reduce the quality of) social, school, or work functioning Other disorders are ruled out Different presentations: ▪ Predominantly inattentive: 6 or more symptoms of inattention, but few symptoms of hyperactivity/ impulsivity ▪ Predominantly hyperactive/impulsive: 6 or more symptoms of hyperactivity/impulsivity, but few symptoms of inattention  DSM V – ADHD Criteria (adults) Adults present a little differently than children: Inattentive symptoms: Hyperactivity/impulsivity symptoms: Careless mistakes at work/school Leaving their seat during Difficulty maintaining attention throughout meetings/lectures lectures or meetings Blurting out answers, finishing Doesn’t seem to listen and thinks of others’ sentences unrelated matters during conversations Interrupting other people, Fail to follow instructions, have difficulty intruding on their activities finishing tasks Struggle to stay quiet during Poor ability to schedule or meet activities deadlines, organize documents, arrange Fidgetting, unable to sit still, sequential tasks constantly moving Procrastinates with tasks that are thought Trouble waiting their turn to be tedious and require sustained Talking excessively attention (i.e. reviewing reports) Feeling restless Loses important things, distractible Forgets scheduled tasks, events DSM V – ADHD Criteria (adults) Instead of needing 6 or more criteria, only 5 or more are necessary ▪ Same stratification into the three presentations Thought that “new-onset” ADHD in adulthood is relatively uncommon (does it exist at all?) ▪ “new-onset” adult ADHD may be: poorly studied, and may actually exist in many patients who do not recall childhood symptoms patients with childhood symptoms that were “masked” ! were problematic only later Although the symptoms cannot be due to another psychiatric or medical illness, adults with confirmed ADHD have a high rate of psychiatric comorbidity ▪ 20 – 40% have a comorbid mood disorder Substance Use Disorders Chronic, relapsing disorder characterized by ▪ Compulsive drug-seeking and drug-taking disorders ▪ Loss of control over drug intake ▪ Negative affect when access to the drug is withheld Can also include physical symptoms and signs Estimated that over 7 million in US have a substance use disorder Relapses are frequent, and morbidity as well as mortality are high ▪ Excess mortality due to overdose and direct or indirect effects (cardiovascular, hepatic, neoplastic, infectious diseases) ▪ Morbidity due to medical conditions (see systems affected above), other psychiatric disorders, and negative impacts on social networks and employment/education Substance Use Disorders – Stages, Theories General stages of addiction: 1. Acute reinforcement and drug use Substances directly or indirectly activate the same neurological systems that are involved in motivation and drive for natural reinforcers (i.e. food) 2. Escalation of drug use/dependence Thought that brain areas involved with acute reinforcement ! long-term changes in certain neuroanatomical regions that underlie habit formation As well, areas in the brain that are involved in executive function and inhibitory control undergo deleterious changes Substance Use Disorders – Stages, Theories General stages of addiction: 3. Late stage – withdrawal/incubation/relapse Long-term changes to networks involved in reward and executive function ! increased likelihood of significant relapse when certain cues are present ▪ social cues, environmental cues ▪ small amounts of a substance ▪ stress These stages can interact with each other, but initially they tend to progress in this order Stages of Substance Use: Neuroanatomy, Neurochemistry Key brain areas: ▪ Midbrain – ventral tegmental area (VTA) – dopaminergic ▪ Nucleus accumbens (NA) – part of the ventral striatum (basal ganglia) – GABA or acetylcholine ▪ Amygdala – rostral to the hippocampus ▪ Hippocampus ▪ Prefrontal cortex ▪ Dorsal striatum i.e. putamen, caudate (basal ganglia)  Stages of Substance Use: Neuroanatomy, Neurochemistry Stage 1 ! acute reinforcement/drug use Mesocorticolimbic pathway is the major reward pathway in humans ▪ Mesolimbic: VTA ! nucleus accumbens ! reinforcement and reward Drugs of abuse cause greater than normal increases in DA release from the VTA ▪ Mesocortical: pathway to the cortex (VTA ! NA ! Ventral pallidum ! prefrontal cortex) Regulation of emotion, executive functions, and cognitive control  Stages of Substance Use: Neuroanatomy, Neurochemistry Stage 1 ! acute reinforcement/drug use Suggested that the reward system is “highjacked” by drugs of abuse ▪ Higher “priority” placed on substances ▪ Less reward from usual reward-eliciting stimuli There are dopamine-independent pathways, but the neuroanatomy for these pathways is likely similar Stage 2 ! Escalation of use and dependence Eventually abnormal circuits get recruited and strengthened: ▪ The dorsal striatum – “habit-forming” areas that become engaged/activated over time (shouldn’t be a reward path)  Stages of Substance Use: Neuroanatomy, Neurochemistry Stage 2 ! Escalation of use and dependence Involvement of the dorsal striatum is thought to be involved in: ▪ Cue-associated drug-seeking and administration ▪ Goal-directed drug-seeking behaviour and craving ▪ Remember – the dorsal striatum Dorsal is mostly involved in regulating striatum movements and habits (not reward) Impairments in prefrontal cortical areas are thought to underly loss of behavioural control and inhibition  Stages of Substance Use: Neuroanatomy, Neurochemistry Stage 2 ! Escalation of use and dependence Involvement of the dorsal striatum is thought to be involved in: ▪ Cue-associated drug-seeking and administration ▪ Goal-directed drug-seeking behaviour Dorsal ▪ May actually be more important striatum in craving than the NA Impairments in prefrontal cortical areas are thought to underly loss of behavioural control and inhibition  Stages of Substance Use: Neuroanatomy, Neurochemistry Stage 3 ! Withdrawal and relapse Again, the VTA (ventral striatum) is involved in all stages of addiction The core centra area of the nucleus accumbens and the prefrontal cortex seem to be the final common pathway driving relapse behaviour Limbic regions – including hippocampus and amygdala – seem to be involved in facilitating cue-related relapses or Dorsal cravings late in the development of striatum addiction The outer portions of the nucleus accumbens, amygdala, and other parts of the limbic lobe seem to be activated by stress-evoked relapse ▪ CRH or cortisol infused in these areas can trigger relapse Neuroanatomy/neurochemistry of ADHD? Very little has been well-proven in humans – animal models aren’t as good as the ones for addiction, multiple theories are applied to neuroimaging findings in humans ▪ A lot of heterogeneity in human findings What seems to be accepted: ▪ Deficits in inhibiting motor responses seem to be associated with deficits in areas in the frontal cortex involved with executive functions, the dorsal striatum (caudate), and the thalamus ▪ Deficits in attention involve similar areas (putamen instead of the striatum) ▪ Challenges with temporal perception/timing likely also include these areas as well as the parietal regions and cerebellum ▪ Many people with ADHD exhibit enhanced reward anticipation/ sensitivity – these involve very similar pathways to substance use disorder (ventral striatum, VTA) Show greater emphasis on immediate vs. delayed rewards Neuroanatomy/neurochemistry of ADHD? Default-mode network is a network that is active “at rest” – cortical areas involved are the medial prefrontal cortex & posterior cingulate cortex (medial parietal lobe) “Alerting-mode” network that maintains attention involves many other regions of the frontal and parietal cortex, as well as the thalamus Thought that those with ADHD have an excessively active default-mode network Neurochemistry of ADHD is unclear – D1 receptors and alpha-adrenoreceptors are the most likely to be impacted/ activated by stimulant medications ▪ Use of stimulant medications changes the amount of dopamine uptake transporters Seems to be fairly lateralized – the networks described above are implicated on the right side of the brain, not left Major References: Baroni A, Castellanos FX. Neuroanatomic and cognitive abnormalities in attention-deficit/ hyperactivity disorder in the era of 'high definition' neuroimaging. Curr Opin Neurobiol. 2015;30:1-8. doi:10.1016/j.conb.2014.08.005 Feltenstein MW, See RE, Fuchs RA. Neural Substrates and Circuits of Drug Addiction. Cold Spring Harb Perspect Med. 2021;11(4):a039628. Published 2021 Apr 1. doi:10.1101/cshperspect.a039628